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1. 发明申请

US20150023870A1 Multiple Signaling Pathways Induced by Hexavalent, Monospecific and Bispecific Antibodies for Enhanced Toxicity to B-Cell Lymphomas and Other Diseases 有权
标题翻译：用于增强B细胞淋巴瘤和其他疾病毒性的六价，单特异性和双特异性抗体诱导的多重信号通路
公开(公告)号：US20150023870A1
公开(公告)日：2015-01-22
申请号：US14491189
申请日：2014-09-19
申请人： Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
IPC分类号： A61K47/48
CPC分类号： A61K47/6807 , A61K39/3955 , A61K47/6811 , A61K47/6813 , A61K47/6815 , A61K47/6849 , A61K47/6851 , A61K47/6867 , A61K47/6885 , A61K51/1027 , A61K51/1045 , C07K14/47 , C07K2317/31 , C07K2317/732 , C07K2317/734 , C07K2319/33 , C07K2319/70 , C07K2319/74
摘要： Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKKα/β and IκBα, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.
摘要翻译：本文公开了包含六价DNL复合物的组合物和使用方法。优选地，复合物包含抗CD20和/或抗-CD22抗体或其片段。更优选地，抗CD20抗体是veltuzumab，抗CD22抗体是依帕珠珠单抗。主题六价DNL复合物的给药诱导疾病如B细胞淋巴瘤或白血病，自身免疫疾病或免疫功能障碍疾病中靶细胞的凋亡和细胞死亡。在最优选的实施方案中，DNL复合物增加磷酸化p38和PTEN的水平，降低磷酸化Lyn，Akt，ERK，IKKα/ bgr的水平; 和Bα，增加RKIP和Bax的表达，并降低靶细胞中Mcl-1，Bcl-xL，Bcl-2和phospho-BAD的表达。受试者DNL复合物显示在低纳摩尔或甚至亚纳摩尔浓度范围内抑制肿瘤细胞生长的EC 50值。

2. 发明申请

US20130164816A1 Methods and Compositions for Generating Bioactive Assemblies of Increased Complexity and Uses 有权
公开(公告)号：US20130164816A1
公开(公告)日：2013-06-27
申请号：US13549906
申请日：2012-07-16
申请人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
IPC分类号： C12N9/96
CPC分类号： A61K47/48438 , A61K31/00 , A61K38/00 , A61K47/48415 , A61K47/48484 , A61K47/485 , A61K47/48538 , A61K47/48546 , A61K47/48561 , A61K47/48569 , A61K47/6811 , A61K47/6817 , A61K47/6829 , A61K47/6833 , A61K47/6843 , A61K47/6845 , A61K47/6849 , A61K47/6851 , A61K2039/505 , B82Y5/00 , B82Y10/00 , B82Y15/00 , C07K14/475 , C07K16/18 , C07K16/22 , C07K16/28 , C07K16/2803 , C07K16/2833 , C07K16/2851 , C07K16/2863 , C07K16/2881 , C07K16/2887 , C07K16/2896 , C07K16/3007 , C07K16/3092 , C07K16/32 , C07K2317/31 , C07K2317/55 , C07K2317/76 , C07K2319/30 , C07K2319/35 , C07K2319/70 , C07K2319/74 , C12N9/12 , C12N9/22 , C12N9/96 , C12Y207/11001 , G01N33/54353 , G01N33/588 , Y02A50/491
摘要： The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

3. 发明申请

US20120276608A1 Multivalent Immunoglobulin-Based Bioactive Assemblies 审中-公开
标题翻译：基于多价免疫球蛋白的生物活性组件
公开(公告)号：US20120276608A1
公开(公告)日：2012-11-01
申请号：US13483761
申请日：2012-05-30
申请人： Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
IPC分类号： C12N9/96
CPC分类号： C07K16/468 , A61K47/6897 , A61K51/088 , B82Y5/00 , B82Y10/00 , C07K16/2803 , C07K16/2887 , C07K16/3007 , C07K16/3092 , C07K2317/31 , C07K2317/55 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/92 , C07K2319/00 , C07K2319/30 , C07K2319/70
摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Preferred embodiments concern hexameric stably tethered structures comprising one or more IgG antibody fragments and which may be monospecific or bispecific. The disclosed methods and compositions provide a facile and general way to obtain stably tethered structures of virtually any functionality and/or binding specificity. The stably tethered structures may be administered to subjects for diagnostic and/or therapeutic use, for example for treatment of cancer or autoimmune disease. The stably tethered structures may bind to and/or be conjugated to a variety of known effectors, such as drugs, enzymes, radionuclides, therapeutic agents and/or diagnostic agents.
摘要翻译：本发明涉及可以具有多种功能和/或结合特异性的限定组合物的稳定的束缚结构的方法和组合物。优选的实施方案涉及包含一种或多种IgG抗体片段并且可以是单特异性或双特异性的六聚体稳定的束缚结构。所公开的方法和组合物提供了实现任何功能和/或结合特异性的稳定的束缚结构的简便和一般的方法。稳定的束缚结构可以施用于受试者用于诊断和/或治疗用途，例如用于治疗癌症或自身免疫性疾病。稳定的束缚结构可以结合到各种已知的效应物上，和/或与其结合，例如药物，酶，放射性核素，治疗剂和/或诊断剂。

4. 发明申请

US20120276100A1 Compositions and Methods of Use of Immunotoxins Comprising Ranpirnase (Rap) Show Potent Cytotoxic Activity 审中-公开
标题翻译：组合物和使用含有兰泼瑞酶（Rapp）的免疫毒素的方法显示强效细胞活性
公开(公告)号：US20120276100A1
公开(公告)日：2012-11-01
申请号：US13528077
申请日：2012-06-20
申请人： Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , Edmund A. Rossi
IPC分类号： C12N9/96 , A61P35/02 , A61P37/00 , A61P37/06 , A61K39/395 , A61P35/00
CPC分类号： C07K16/2803 , B82Y5/00 , B82Y10/00 , C07K16/2833 , C07K16/2863 , C07K16/2887 , C07K16/3007 , C07K16/3092 , C07K2317/24 , C07K2317/55 , C07K2317/77 , C07K2319/70
摘要： The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 or anti-CD22 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.
摘要翻译：本发明涉及用于形成具有高效力和低全身毒性的免疫毒素复合物的方法和组合物。在优选的实施方案中，毒素部分是兰普瑞酶（Rap），例如Rap（Q）。在更优选的实施方案中，免疫毒素使用对接 - 锁（DNL）技术制备。与单独的毒素，单独的抗体，未缀合的毒素加抗体或甚至其它类型的毒素 - 抗体构建体相比，免疫毒素表现出改进的药代动力学，具有较长的血清半衰期和显着更高的功效。在最优选的实施方案中，构建体包含与Rap结合的抗Trop-2或抗-CD22抗体，尽管抗体，抗体片段和毒素的其它组合可用于形成受试者免疫毒素。免疫毒素可用于治疗各种疾病，例如癌症，自身免疫性疾病或免疫功能障碍。

5. 发明申请

US20120196346A1 Methods for Generating Stably Linked Complexes Composed of Homodimers, Homotetramers or Dimers of Dimers and Uses 有权
标题翻译：用于产生由同型二聚体，同分子或二聚体和用途的二聚体组成的稳定连接的复合物的方法
公开(公告)号：US20120196346A1
公开(公告)日：2012-08-02
申请号：US13419614
申请日：2012-03-14
申请人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
IPC分类号： C07K19/00 , C12N9/96
CPC分类号： C12N9/12 , B82Y5/00 , B82Y10/00 , C07K16/18 , C07K16/2803 , C07K16/2887 , C07K16/3007 , C07K16/3092 , C07K2317/31 , C07K2317/55 , C07K2319/00 , C07K2319/70 , C12Y207/11011
摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.
摘要翻译：本发明涉及可以具有多种功能和/或结合特异性的限定组合物的稳定的束缚结构的方法和组合物。具体实施方案涉及包含单体的同型二聚体，其含有连接到前体的二聚化和对接结构域。前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白的片段，蛋白质或其他分子的已知配体，酶，可检测标记或标签，治疗剂，毒素，药物，细胞因子，白细胞介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米颗粒，量子点，有机或无机化合物等。其他实施方案涉及四聚体，和第二同二聚体，其可以相同或不同。所公开的方法和组合物提供了获得实质上任何功能性和/或结合特异性的同源二聚体，同源四聚体和异源四聚体的简便且一般的方式。

6. 发明申请

US20120196326A1 Mammalian Cell Lines for Increasing Longevity and Protein Yield from a Cell Culture 有权
标题翻译：哺乳动物细胞系从细胞培养增加寿命和蛋白质产量
公开(公告)号：US20120196326A1
公开(公告)日：2012-08-02
申请号：US13413871
申请日：2012-03-07
申请人： David M. Goldenberg , Zhengxing Qu , Chien Hsing Chang , Edmund A. Rossi , Jeng-Dar Yang , Diane Nordstrom
发明人： David M. Goldenberg , Zhengxing Qu , Chien Hsing Chang , Edmund A. Rossi , Jeng-Dar Yang , Diane Nordstrom
IPC分类号： C12P21/00 , C12N9/00
CPC分类号： C07K16/2896 , A61K2039/505 , C07K14/005 , C07K14/4747 , C07K16/00 , C07K16/18 , C07K16/2803 , C07K16/3007 , C07K2317/24 , C07K2317/31 , C12N5/0694 , C12N15/85 , C12N15/86 , C12N2500/90 , C12N2501/48 , C12N2510/02 , C12N2710/20022 , C12N2740/10043 , C12P21/02
摘要： Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.
摘要翻译：公开了用于增加细胞培养物的寿命并允许增加蛋白质生产的组合物和方法，优选重组蛋白，例如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素和疫苗。用凋亡抑制基因或载体如三重突变体Bcl-2基因转染的细胞可以在培养物中更长时间地存活，导致蛋白质生物合成的状态和产量的延长。这样的转染细胞表现出最大的细胞密度，其等于或超过由亲本细胞系实现的最大密度。转染的细胞也可以预先适应于无血清培养基中生长，大大减少了在无血清培养基中获得蛋白质产生所需的时间。在某些方法中，预先调节的细胞可以在无血清条件下转化后用于蛋白质生产。该方法优选涉及真核细胞，更优选哺乳动物细胞。

7. 发明授权

US08163291B2 Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses 有权
标题翻译：用于产生由同型二聚体，同三聚体或二聚体二聚体和用途组成的稳定连接络合物的方法
公开(公告)号：US08163291B2
公开(公告)日：2012-04-24
申请号：US12468589
申请日：2009-05-19
申请人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
IPC分类号： A61K39/385 , A61K39/44 , A61K39/00 , A61K39/395
CPC分类号： C12N9/12 , B82Y5/00 , B82Y10/00 , C07K16/18 , C07K16/2803 , C07K16/2887 , C07K16/3007 , C07K16/3092 , C07K2317/31 , C07K2317/55 , C07K2319/00 , C07K2319/70 , C12Y207/11011
摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.
摘要翻译：本发明涉及可以具有多种功能和/或结合特异性的限定组合物的稳定的束缚结构的方法和组合物。具体实施方案涉及包含单体的同型二聚体，其含有连接到前体的二聚化和对接结构域。前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白的片段，蛋白质或其他分子的已知配体，酶，可检测标记或标签，治疗剂，毒素，药物，细胞因子，白细胞介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米颗粒，量子点，有机或无机化合物等。其他实施方案涉及四聚体，和第二同二聚体，其可以相同或不同。所公开的方法和组合物提供了获得实质上任何功能性和/或结合特异性的同源二聚体，同源四聚体和异源四聚体的简便且一般的方式。

8. 发明申请

US20110300105A1 Dimeric Alpha Interferon PEGylated Site-Specifically Shows Enhanced and Prolonged Efficacy in Vivo 有权
标题翻译：二聚体阿尔法干扰素聚乙二醇化位点 - 具体显示体内增强和延长功效
公开(公告)号：US20110300105A1
公开(公告)日：2011-12-08
申请号：US13178092
申请日：2011-07-07
申请人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
IPC分类号： A61K38/21 , A61P35/00 , A61P37/06 , A61P31/12
CPC分类号： C12N9/1205 , A61K39/395 , A61K47/60 , A61K47/64 , B82Y10/00 , B82Y30/00 , C07K16/00 , C07K16/005 , C07K16/283 , C07K16/3007 , C07K16/468 , C07K2317/31 , C07K2317/55 , C07K2317/73 , C07K2319/00 , C07K2319/70 , Y02A50/386
摘要： The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two therapeutic agents and one PEG moiety. In alternative embodiments, the therapeutic agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one therapeutic agent. In more preferred embodiments, the therapeutic agent may comprise any peptide or protein of physiologic or therapeutic activity, preferably a cytokine, more preferably interferon-α2b. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.
摘要翻译：本发明涉及用于形成定义化学计量和结构的聚乙二醇化配合物的方法和组合物。在优选的实施方案中，使用对接和锁定技术形成聚乙二醇化复合物，通过将治疗剂连接到DDD序列并将PEG部分连接到AD序列并允许DDD序列以2： 1化学计量，以形成具有两个治疗剂和一个PEG部分的PEG化复合物。在替代实施方案中，治疗剂可以连接到AD序列，并将PEG连接到DDD序列以与两个PEG部分和一种治疗剂形成聚乙二醇化复合物。在更优选的实施方案中，治疗剂可以包含生理或治疗活性的任何肽或蛋白质，优选细胞因子，更优选干扰素-α2b。当注射到受试者中时，聚乙二醇化复合物表现出明显较慢的清除率，并且可用于治疗各种各样的疾病。

9. 发明授权

US07785880B2 Mammalian cell lines for increasing longevity and protein yield from cell culture 有权
标题翻译：哺乳动物细胞系增加细胞培养的寿命和蛋白质产量
公开(公告)号：US07785880B2
公开(公告)日：2010-08-31
申请号：US12405733
申请日：2009-03-17
申请人： David M. Goldenberg , Zhengxing Qu , Chien-Hsing Chang , Edmund A. Rossi , Jeng-Dar Yang , Diane Nordstrom
发明人： David M. Goldenberg , Zhengxing Qu , Chien-Hsing Chang , Edmund A. Rossi , Jeng-Dar Yang , Diane Nordstrom
IPC分类号： C12N5/00 , C12N15/00 , C12P21/00
CPC分类号： C07K16/2896 , A61K2039/505 , C07K14/005 , C07K14/4747 , C07K16/00 , C07K16/18 , C07K16/2803 , C07K16/3007 , C07K2317/24 , C07K2317/31 , C12N5/0694 , C12N15/85 , C12N15/86 , C12N2500/90 , C12N2501/48 , C12N2510/02 , C12N2710/20022 , C12N2740/10043 , C12P21/02
摘要： Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.
摘要翻译：公开了用于增加细胞培养物的寿命并允许增加蛋白质生产的组合物和方法，优选重组蛋白，例如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素和疫苗。用凋亡抑制基因或载体如三重突变体Bcl-2基因转染的细胞可以在培养物中更长时间地存活，导致蛋白质生物合成的状态和产量的延长。这样的转染细胞表现出最大的细胞密度，其等于或超过由亲本细胞系实现的最大密度。转染的细胞也可以预先适应于无血清培养基中生长，大大减少了在无血清培养基中获得蛋白质产生所需的时间。在某些方法中，预先调节的细胞可以在无血清条件下转化后用于蛋白质生产。该方法优选涉及真核细胞，更优选哺乳动物细胞。

10. 发明授权

US07550143B2 Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses 有权
标题翻译：用于产生由同型二聚体，同三聚体或二聚体二聚体和用途组成的稳定连接络合物的方法
公开(公告)号：US07550143B2
公开(公告)日：2009-06-23
申请号：US11389358
申请日：2006-03-24
申请人： Chien Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
发明人： Chien Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
IPC分类号： C07K16/46 , C07K16/28 , C07K16/30 , A61K38/01 , A61K38/19 , A61K39/395
CPC分类号： C12N9/12 , B82Y5/00 , B82Y10/00 , C07K16/18 , C07K16/2803 , C07K16/2887 , C07K16/3007 , C07K16/3092 , C07K2317/31 , C07K2317/55 , C07K2319/00 , C07K2319/70 , C12Y207/11011
摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.
摘要翻译：本发明涉及可以具有多种功能和/或结合特异性的限定组合物的稳定的束缚结构的方法和组合物。具体实施方案涉及包含单体的同型二聚体，其含有连接到前体的二聚化和对接结构域。前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白的片段，蛋白质或其他分子的已知配体，酶，可检测标记或标签，治疗剂，毒素，药物，细胞因子，白细胞介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米颗粒，量子点，有机或无机化合物等。其他实施方案涉及四聚体，和第二同二聚体，其可以相同或不同。所公开的方法和组合物提供了获得实质上任何功能性和/或结合特异性的同源二聚体，同源四聚体和异源四聚体的简便且一般的方式。

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